The retina is a multilayered tissue that lines the concave (inner) surface of the back of the eye. Photoreceptor cells within the retina are activated by light that enters the eye and convert the light signals into electrochemical signals that are conveyed to retinal neurons. The retinal neurons, in turn, relay the signals to the visual centers of the brain via the optic nerve, thereby allowing the brain to perceive visual images. Photoreceptor cells are broadly categorized as rod cells and cone cells (named for their shape). Whereas cone cells contain photopigments that are necessary for color vision, rod cells contain a photopigment, rhodopsin, that is highly sensitive to light and thus allows vision under dim light conditions (e.g., night). A rod cell is sensitive enough to become activated by a single photon of light, whereas a cone cell requires tens to hundreds of photons to become activated.
Rhodopsin, the photoreceptive pigment of rod cells, undergoes a conformational change when activated by a photon of light. Rhodopsin consists of a seven-pass transmembrane protein called opsin that is covalently bound to a prosthetic group called retinal, a derivative of vitamin A. Non-activated retinal exists in the 11-cis form, whereas stimulation by light induces a conformational change to the all-trans form. The conformational change in retinal induces a corresponding conformational change in the covalently bound opsin polypeptide, thereby triggering a second messenger cascade within the photoreceptor cell that results in the transmission of signals to the appropriate retinal neurons. These signals are transmitted along the optic nerve to the visual centers of the brain, which allows the brain to process the visual input and perceive a visual image.
Various diseases and conditions that destroy photoreceptor cells of the retina cause partial or full vision loss. Two major diseases of the retina are age-related macular degeneration (AMD) and retinitis pigmentosa (RP). As the leading cause of vision loss and blindness in older adults, AMD causes both rod and cone photoreceptor cells, located within the macula at the center of the retina, to deteriorate. Furthermore, AMD affects central vision and thus causes difficulty with reading, driving, and other tasks that require high-contrast vision.
The latter disease, RP, is an inherited condition in which the rod photoreceptor cells degenerate, thereby causing vision loss and blindness. The loss of rod cells impairs the ability to see in dim light and gradually reduces peripheral vision until the patient suffers from tunnel vision and, ultimately, blindness.
To date, a number of artificial retina prototypes have been investigated for the treatment of such retinal diseases and conditions, but each has distinct disadvantages. One of the more promising designs, a subretinal implant from Optobionics, employs a silicon diode material to generate electrical stimulation upon light activation. The silicon diode photoreceptor, however, only generates a sufficient current when intense light is used as stimulation and provides only dim vision in the brightest settings. An alternative design is an epiretinal implant designed by researchers at the University of Southern California that employs the use of an external camera, mounted on a pair of glasses, connected to a microelectrode array by a connecting cable. The electrode array provides electrical stimulation directly to the ganglion cells. In clinical trials, a subject was able to perceive light on all 16 electrodes of the array, detect motion, and recognize simple shapes. This design has a distinct disadvantage in that it requires external hardware, such as glasses and the surgically implanted external device.
What is needed are improved and less surgically invasive retinal implants that can at least partially restore vision to patients suffering from vision loss resulting from the loss of photoreceptor cells as a consequence of retinal disease or damage.